Document Type
Article
Publication Date
10-8-2025
Identifier
DOI: 10.1016/j.xgen.2025.100977
Abstract
The NPIP gene family is among the most positively selected gene families in humans/apes and drives independent duplication in primate lineages. These duplications promote genetic instability, leading to recurrent disease-associated microduplication and microdeletion syndromes. Despite its importance, little is known about its function or variation in humans, as short-read sequencing cannot distinguish high-identity duplications. Using long-read assemblies of 169 human haplotypes, we find extreme variation in the content and organization of NPIP loci. We identify fixed and polymorphic paralogs and observe ongoing positive selection. With long-read RNA sequencing (RNA-seq), we create paralog-specific gene models, the majority of which were not previously documented, and observe paralog-specific tissue specificity. This analysis of an exceptionally dynamic gene family provides candidates for future functional study.
Journal Title
Cell Genom
Volume
5
Issue
10
First Page
100977
Last Page
100977
MeSH Keywords
Humans; Selection, Genetic; Genome, Human; Multigene Family; Haplotypes; Animals; Genetic Variation; Evolution, Molecular
PubMed ID
40848717
Keywords
copy-number variation; human evolution; segmental duplication; structural genomic variation
Recommended Citation
Dishuck PC, Munson KM, Lewis AP, et al. Structural variation, selection, and diversification of the NPIP gene family from the human pangenome. Cell Genom. 2025;5(10):100977. doi:10.1016/j.xgen.2025.100977
Comments
Grants and funding
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Publisher's Link: https://linkinghub.elsevier.com/retrieve/pii/S2666-979X(25)00233-2